What Is USP <665>?
USP <665> is a United States Pharmacopeia standard that provides guidance for evaluating Extractables and Leachables (E&L) from polymeric materials used in pharmaceutical manufacturing and processing, especially in single-use systems.
For biopharmaceutical end users, its main purpose is to help assess whether plastic components such as tubing, bags, connectors, sensors, filters, or assemblies may release chemicals into a product during use. The chapter outlines a framework for risk assessment, material characterization, and extractables testing, so manufacturers can better understand the potential impact of these materials on product quality and patient safety.
It is especially relevant for drug manufacturers using single-use technologies because these systems rely heavily on polymer-based components. The USP chapter helps users compare suppliers, identify potential risks earlier, and build a more consistent evidence package for product development and validation.
In short, USP <665> is a tool for managing material-related risk in bioprocessing by standardizing how polymeric single-use materials are assessed for chemical compatibility and safety.
To support our customers’ extractables and potential leachables programs, we commissioned a comprehensive USP <665> -compliant analysis of the extractables profile of all fluid-contact materials used in the qualification of our Ingold Single-Use Sensor (InSUS) line, which is designed for integration into single-use bioreactors and mixing containers.
The sensors were evaluated after gamma irradiation (> 45 kGy) and subjected to a single extraction condition using a 50% ethanol solution for 24 hours at 40°C, with a surface-area-to-extraction-volume ratio of 6 cm² per mL. The analytical methods employed included UPLC-DAD/MS, DI-GC/MS, and HS-GC/MS.
Our USP <665> compliant extractable study:
Provides a standardized extractables profile generated for our InSUS single-use sensor line
Helps our customers with early risk assessment and supplier comparison
Can reduce the need for starting from scratch in qualification work
Supports regulatory documentation and internal reviews
Gives insight into potential leachables of concern under defined test conditions
Extractables are generated under worst-case laboratory conditions, not necessarily real process conditions. It does not replace product-specific leachable studies designed for real application environments.
End users still need to assess:
For further information, please contact your METTLER TOLEDO sales representative.
For more details on our InSUS sensor series for pH and dissolved oxygen in-line measurement, go to: www.mt.com/insus_pH and www.mt.com/insus_DO
Topics covered in this guide are:
Dr. Stefan Bardeck brings more than two decades of process analytics expertise to METTLER TOLEDO. With a Ph.D. in Technical and Polymer Chemistry, Stefan bridges the gap between material science and practical inline measurement. Having held leadership roles across multiple industries - including pharma, chemical, and food & beverage - his primary focus today is driving single-use sensor innovation for biopharma applications.
